Why the study?
SGLT2 inhibitors confer cardiovascular benefits beyond glycemic control, motivating a review of potential mechanisms linking them to the modulation of ischemia-reperfusion injuries and wider indications.
What are the potential mechanisms by which SGLT2 inhibitors modulate ischemia-reperfusion injuries?
What are the potential mechanisms by which SGLT2 inhibitors modulate ischemia-reperfusion injuries?
This review summarizes the potential cardioprotective mechanisms of SGLT2 inhibitors in ischemia-reperfusion injury, highlighting NHE inhibition and metabolic shifts as key pathways beyond glycemic control.
Answers are grounded in this paper and cite their sources.
May inform mechanistic research on SGLT2 inhibitors beyond glycemic effects; leaves open clinical translation in ischemia-reperfusion injury.
Recently added to the therapeutic arsenal against chronic heart failure as a first intention drug, the antidiabetic drug-class sodium-glucose cotransporter-2 inhibitors (SGLT2i) showed efficacy in decreasing overall mortality, hospitalization, and sudden death in patients of this very population, in whom chronic or acute ischemia count among the first cause. Remarkably, this benefit was observed independently from diabetic status, and benefited both preserved and altered ventricular ejection fraction. This feature, observed in several large randomized controlled trials, suggests additional effects from SGLT2i beyond isolated glycemia control. Indeed, both in-vitro and animal models suggest that inhibiting the Na(+)/H(+ )exchanger (NHE) may be key to preventing ischemia/ reperfusion injuries, and by extension may hold a similar role in ischemic damage control and ischemic preconditioning. Yet, several other mechanisms may be explored which may help better target those who may benefit most from SGLT2i molecules. Because of a large therapeutic margin with few adverse events, ease of prescription and potential pharmacological efficacity, SGLT2i could be candidate for wider indications. In this review, we aim to summarize all evidence which link SGLT2i and ischemia/reperfusion injuries modulation, by first listing known mechanisms, including metabolic switch, prevention of lethal arrythmias and others, which portend the latter, and second, hypothesize how the former may interact with these mechanisms.
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Quentin et al. (2022) studied this question.
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